Serum C-terminal Cross-linking Telopeptide Research Articles

Bone turnover markers and bone mineral density response with risedronate therapy: Relationship with fracture risk and patient adherence

Surrogate markers of fracture risk--bone turnover markers (BTMs) and bone mineral density (BMD)--can be used to monitor treatment response. We assessed whether changes in these markers greater than the least significant change (LSC) were associated with fracture risk reduction and greater adherence. This secondary analysis of the Improving Measurements of Persistence on ACtonel Treatment (IMPACT) study--a multinational prospective, open-label, cluster-randomized study of postmenopausal women on oral risedronate 5 mg/d for 52 weeks-assessed adherence by electronic monitors. Urinary N-terminal cross-linked telopeptide of type 1 collagen (uNTX) and serum C-terminal cross-linked telopeptide of type 1 collagen (sCTX) levels were assessed at baseline and weeks 10 and 22, and BMD at baseline and week 52. Fractures were recorded as adverse events. In 2302 women, responses beyond LSC in BTMs (uNTX and sCTX) and BMD (spine only) were associated with a reduced risk of nonvertebral fractures (NVFs) and all fractures. NVF incidence was about 50% lower in patients with 30% or more of uNTX reduction at week 22 (1.6%) than in those with less than 30% reduction (3.2%, p = .015). NVFs also were reduced in patients with more than 3% spine BMD increase at 52 weeks than those with 3% or less. Responses greater than LSC in BTMs and BMD were associated with greater adherence, but there was no association between adherence and fracture outcomes at 52 weeks. Changes greater than the LSC in BTMs and BMD reflect better treatment adherence, were associated with fracture risk reduction, and identify differences in individual responsiveness to risedronate.

Effects of pharmaceutical care on adherence and persistence to bisphosphonates in postmenopausal osteoporotic women

Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy, but the association between adherence and bone turnover markers (BTMs) has never been studied. Therefore, the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence (and its effects on BTMs), as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates. A randomized controlled trial was conducted from 2005 to 2009 in the University Malaya Medical Centre, Malaysia. postmenopausal osteoporotic women diagnosed with osteoporosis with a T-score ≤ -2·5 or who had a low-trauma fracture and prescribed weekly alendronate/risedronate. Intervention participants received counselling on osteoporosis, risk factors, lifestyle modifications, goals of therapy, side effects and the importance of adherence. Adherence was assessed at months 3, 6 and 12, and persistence at month 12. Feedback on BTMs was provided at months 4 and 7. The control group received no counselling. Two BTMs were used: serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) and serum osteocalcin (OC). medication adherence, BTMs and persistence. Intervention participants who received pharmaceutical care reported significantly higher medication adherence at 6 (P = 0·015) and 12 months (P = 0·047) compared with the control group; but this effect was not shown by the BTMs. This is probably due to the long effect of bisphosphonates in bone. A significant difference was found between serum CTX-I and OC in identifying non-responders to anti-resorptive therapy (P < 0·001), indicating the usefulness of BTMs as an objective marker. However, pharmaceutical care did not affect persistence to osteoporosis therapy within a 1-year period [log rank (Mantel-Cox) χ² = 0·496, P = 0·481]. The proportion of participants who were persistent with bisphosphonate therapy after 12 months was 89·8% and 87·0% in the control and intervention group respectively. The provision of pharmaceutical care improved medication adherence but not persistence. BTMs were not appropriate objective measures for assessing adherence to weekly bisphosphonates but were useful for identifying non-responders to treatment within 3-6 months, much earlier than using bone mineral density. The study indicates that pharmacists have a role in improving medication adherence, but its long-term effect on persistence warrants further studies with longer duration.

Relationship between spine osteoarthritis, bone mineral density and bone turn over markers in post menopausal women

BackgroundSeveral studies have observed an inverse relationship between osteoporosis and spinal osteoarthritis, the latter being considered as possibly delaying the development of osteoporosis. The aim of this study was to determine the association between individual radiographic features of spine degeneration, bone mineral density (BMD) and bone-turn over markers.MethodsIt was a cross sectional study of 277 post menopausal women. BMD of all patients was assessed at the spine and hip using dual-energy X-ray absorptiometry. Lateral spinal radiographs were evaluated for features of disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes and disc space narrowing (DSN). For Bone turn-over markers, we assessed serum osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTX). Linear regressions and partial correlation were used respectively to determine the association between each of disc degeneration features, BMD, and both CTX and osteocalcin.ResultsMean age of patients was 58.7 ± 7.7 years. Eighty four patients (31.2%) were osteoporotic and 88.44% had spine osteoarthritis. At all measured sites, there was an increase in BMD with increasing severity of disc narrowing while there was no association between severity of osteophytes and BMD. After adjustment for age and BMI, there was a significant negative correlation between CTX and DSN. However, no significant correlation was found between CTX and osteophytes and between osteocalcin and both osteophytes or DSN.ConclusionIn post menopausal women the severity of disc narrowing, but not osteophytes, is associated with a generalized increase in BMD and a decreased rate of bone resorption. These results are consistent with the hypothesis that osteoarthritis, through DSN, has a protective effect against bone loss, mediated by a lower rate of bone resorption. However, spine BMD is not a relevant surrogate marker for the assessment of osteoporosis in the spine in patients with osteoarthritis and debate as to the relationship between OA and OP is still open because of the contradictory data in the literature.

Vitamin D deficiency does not alter biochemical markers of bone metabolism before or after autograft in patients with multiple myeloma

So far, only one study has demonstrated a high incidence of vitamin D deficiency in patients with multiple myeloma. Vitamin D deficiency may alter bone remodelling in myeloma. In this study, we aimed to determine the prevalence of vitamin D deficiency and to assess its impact on bone remodelling and bone mineral density before and after autologous stem cell transplantation (ASCT). In 39 consecutive patients receiving high-dose chemotherapy (melphalan 200 mg/m(2)) followed by ASCT for multiple myeloma, we measured before (T0) and 12 months after ASCT (T12) serum calcium, 25-OH-D, PTH 1-84, bone alkaline phosphatase (bALP), serum C-terminal cross-linking telopeptide and lumbar spine bone mineral density (BMD). Mean vitamin D levels were low: 15 +/- 5 ng/mL (9-18) at T0 and 16 +/- 5 ng/mL (14-22) at T12. Twenty-six patients (68%) had vitamin D deficiency (25-OH-D < 20 ng/mL) at T0 and 58% at T12. Patients in the vitamin D-deficient group had higher serum PTH levels than those in the vitamin D-sufficient group : 71 +/- 24 pg/mL vs. 52 +/- 18 pg/mL (P = 0.04). Biochemical bone markers were identical in both groups at T0 and T12. Z-score values did not significantly differ between the two groups at T0 and T12. There were no correlations between 25-OH-D and BMD or bone marker levels. Vitamin D deficiency does not impair biochemical markers of bone metabolism in patients with multiple myeloma, before or after ASCT.

Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women

Osteoporosis is a severe condition in postmenopausal women and a common cause of fracture. Osteoporosis is a complex disease with a strong genetic impact, but susceptibility is determined by many genes with modest effects and environmental factors. Only a handful of genes consistently associated with osteoporosis have been identified so far. Inflammation affects bone metabolism by interfering with the interplay between bone resorption and formation, and many inflammatory mediators are involved in natural bone remodeling. The cytokine macrophage migration inhibitory factor (MIF) has been shown to affect bone density in rodents, and polymorphisms in the human MIF promoter are associated with inflammatory disorders such as rheumatoid arthritis. We investigated the association of polymorphisms in the MIF gene with bone mineral density (BMD) and bone loss in 1002 elderly women using MIF promoter polymorphisms MIF-CATT 5 – 8 and rs755622(G/C) located −794 and −173 bp upstream of the transcriptional start site. Bone loss was estimated both by the change in BMD over 5 years and by the levels of bone resorption markers in serum measured at four occasions during a 5-year period. The MIF-CATT 7/rs755622(C) haplotype was associated with increased rate of bone loss during 5 years at the femoral neck ( p < 0.05) and total hip ( p < 0.05). In addition, the MIF-CATT 7/rs755622(C) haplotype carriers had higher levels of the bone turnover marker serum C-terminal cross-linking telopeptide of type I collagen (S-CTX-I, p < 0.01) during the 5 year follow-up period. There was no association between MIF-CATT 7/rs755622(C) and baseline BMD at femoral neck, total hip or lumbar spine. We conclude that MIF promoter polymorphisms have modest effects on bone remodeling and are associated with the rate of bone loss in elderly women.

Correlation Between Serum C-Terminal Cross-Linking Telopeptide of Type I Collagen and Staging of Oral Bisphosphonate-Related Osteonecrosis of the Jaws

The aim of the present study was to correlate the staging of bisphosphonate-related osteonecrosis of the jaws (BRONJ) with serum C-terminal cross-linking telopeptide of type I collagen (CTX), which is under debate as an index of risk prediction. Stage I BRONJ was defined as asymptomatic osteonecrotic bone. Stage II BRONJ includes infection, and stage III includes additional complications such as fracture or extraoral fistulas. The serum CTX values of 18 patients (mean age 74 years) who were diagnosed with osteonecrosis of the jaws caused by oral bisphosphonate were investigated. The serum CTX values ranged from 10 to 262 pg/mL (mean 112 +/- 76.1). The mean duration of bisphosphonate therapy was 3.9 years, and 17 of the 18 patients had received once weekly 70 mg aldendronate and 1 patient once weekly 35 mg risedronate. The risk assessment was rated according to the CTX values of the individual patient (minimal risk, more than 150 pg/mL; moderate, 100 to 150 pg/mL; and high, less than 100 pg/mL). Next, the BRONJ scores were calculated according to the number of the BRONJ lesions and their stage. The risk assessment and BRONJ scores were correlated. The result was statistically significant (P = .019). BRONJ is relatively rare but has been increasingly recognized in our clinic. The usefulness of the serum CTX value as an index of risk prediction continues to be debated. Considering the staging of lesions and the number of lesions, we found a significant correlation between the disease severity and the risk assessment using serum CTX.

Serum homocysteine, folate and vitamin B12 in patients with Paget’s disease of bone: the effect of zoledronic acid

High serum homocysteine (HCY) and indirectly deficiency of folate and/or vitamin B(12) stimulate bone resorption and adversely affect collagen cross-linking. The aim of this study was the evaluation of serum levels of HCY, folate and vitamin B(12) in patients with Paget's disease of bone (PDB) and the effect of zoledronic acid (ZOL) on their serum levels. Nine consecutive patients with polyostotic PDB (median age 66 years) received a single 5-mg ZOL infusion. Blood samples for HCY, folate, vitamin B(12), 25-hydroxyvitamin D (25-OH-D), total serum alkaline phosphatase (TSAP), bone-specific serum alkaline phosphatase (BSAP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were obtained at baseline and 3, 6 and 12 months after ZOL infusion. Twelve age-, gender- and BMI-matched healthy individuals were recruited for the control group at baseline assessment. Patients with PDB had significantly higher serum HCY (p = 0.028), folate (p < 0.001) and bone markers [TSAP (p < 0.001), BSAP (p < 0.001) and CTX (p < 0.001)] compared with the control group at baseline. In the pagetic group, serum HCY significantly decreased 3 months after ZOL infusion and remained essentially unchanged up to the end of the study (p = 0.005). Serum vitamin B(12) and folate remained unaffected throughout the study. Our data suggest that serum HCY levels are increased in patients with PDB. A single ZOL infusion results in a decrease in HCY levels that might represent another mechanism for the reduction of the activity of PDB achieved by ZOL.

Transient secondary hyperparathyroidism following intravenous infusion of zoledronic acid

Dear Editor, We have read with interest the paper of Sayin and Yazici [1], describing a case of secondary hyperparathyroidism following multiple intravenous zoledronic acid (ZOL) infusions in a patient with stomach lymphoma and bone metastases. The authors supported that serum parathyroid hormone (PTH) continued to increase, despite serum calcium and vitamin D normalization, until ZOL infusions were stopped. Hypocalcemia has been described after ZOL, as well as after other bisphosphonates (BPs), in various conditions, including bone metastases, Paget’s disease of bone (PDB), and osteoporosis. Transient secondary hyperparathyroidism after a single ZOL infusion has previously been observed in a cohort of nine patients with active PDB [2]. These patients had normal serum calcium, magnesium, and vitamin D and no evidence of hyperparathyroidism or hypoparathyroidism at baseline. They had received calcium carbonate (1,500 mg) and vitamin D (400 IU) daily for 10 days before, as well as after the infusion, until serum calcium was normalized. ZOL effectively restricted PDB activity, as it was shown by the significant reduction in total serum alkaline phosphatase (322±211 IU/L at baseline vs. 101±36 IU/L at 3 months vs. 93±42 IU/L at 12 months) and in the scintigraphic index of involvement, a dimensionless marker for the per patient activity of the disease (14.4±7.6 vs. 7.2±1.8 vs. 5.5±2.5, respectively) and the scintigraphic ratio, a dimensionless marker for the per lesion activity of the disease (12.8±7.7 vs. 7.0±2.9 vs. 5.8±3.0, respectively) [2]. Other bone turnover markers, such as bone-specific serum alkaline phosphatase and C-terminal cross-linking telopeptide of type I collagen (CTX), follow a similar pattern of reduction, as it has been shown elsewhere [3]. However, a significant hypocalcemia [decrease of 10% (range 4–23%) in the mean serum calcium] on the third day (2.43±0.13 vs. 2.18±0.10 mmol/L at baseline, p<0.05) was observed accompanied by a mild but not statistically significant hypophosphatemia. No patient experienced symptoms or signs of hypocalcemia. Interestingly, PTH remained significantly increased by 90% (range 20–252%) 3 months (11.6±8.7 vs. 6.8±5.7 pmol/L at baseline, p<0.05) after ZOL infusion and returned to baseline levels at 12 months (7.5±4.8 pmol/L, p=ns vs. baseline), although calcium was normalized by the tenth day (2.35±0.13 mmol/L, p=ns vs. baseline) in all patients [2]. It seems that PTH increase after treatment is compensatory in order to maintain normocalcemia. The ability of the parathyroid gland to react prevents long-term hypocalcemia, by increasing renal reabsorption of calcium and vitamin D production and by stimulating osteoclasts. The effect of PTH on osteoclasts is restricted in patients taking BPs, depending on the potency of the BP. The newer more potent aminobisphosphonates, such as ZOL, initially create a bone remodeling imbalance by strongly suppressing bone S. A. Polyzos Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece

Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

BackgroundSkeletal uptake of 99mTc labelled methylene diphosphonate (99mTc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99mTc-MDP.Methods22 postmenopausal women (52–80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99mTc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC).ResultsThe median TSU of 99mTc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density.ConclusionIn conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99mTc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption.

Assessment of Circulating Dickkopf-1 with a New Two-Site Immunoassay in Healthy Subjects and Women with Breast Cancer and Bone Metastases

The aim of our study was to investigate the sex- and age-related changes of serum Dickkopf-1 (Dkk-1), a soluble inhibitor of the Wnt signaling pathway, in healthy individuals and in patients with breast cancer (BC) and bone metastases (BM) using a new ELISA. Association of serum Dkk-1 with markers of bone turnover was also investigated. Serum Dkk-1 measurements were performed using a commercial sandwich ELISA in 150 healthy men, 175 healthy pre- and postmenopausal women (20-65 years), 22 women with BC and BM (mean age 63 years), and 16 women with BC and metastases at sites other than bone (mean age 53 years). Intra- and interassay coefficients of variation were below 7% and 12%, respectively. The detection limit was determined to be 0.018 microg/L. In healthy women and men, Dkk-1 did not change with age. Serum Dkk-1 modestly correlated with serum bone alkaline phosphatase (r = 0.19, P = 0.013) and serum C-terminal cross-linking telopeptide of type I collagen (r = 0.19, P = 0.014) in women but not in men. Dkk-1 levels were higher in women with BC and BM (5.57 +/- 5.50 microg/L) than in healthy age-matched controls (3.47 +/- 1.47 microg/L, P < 0.0001) and women with metastases at sites other than bone (3.57 +/- 1.66 microg/L, P = 0.0003). In conclusion, serum Dkk-1 is stable with age in healthy women and men and increases in patients with BC and BM. Measurements of circulating Dkk-1 with this new ELISA may be useful for the clinical investigation of patients with malignant bone diseases.

Monthly ibandronate suppresses serum CTX-I within 3 days and maintains a monthly fluctuating pattern of suppression

Bone turnover markers such as serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) can be used to assess drug efficacy in osteoporosis. This study evaluated the pattern of CTX-I suppression in postmenopausal osteoporotic women receiving ibandronate. Ibandronate decreased serum CTX-I levels within 3 days of therapy initiation. Over 6 months, the levels remained suppressed below baseline. This randomized, double-blind, placebo-controlled study evaluated the rapidity of onset and pattern of suppression of the bone resorption marker serum CTX-I in women with postmenopausal osteoporosis (PMO) who received once-monthly oral ibandronate. Women diagnosed with PMO received once-monthly oral ibandronate (150 mg) or placebo for 6 months. Serum CTX-I was measured at baseline and after study dose administration on day 3 (month 1 only) and days 7, 14, 21, and 28 (months 1-6). Bone-specific alkaline phosphatase was measured on days 7 and 28 (months 1-6). This study enrolled 67 women: 49 received ibandronate, 17 received placebo, and one took no study drug. At day 3, median reduction in serum CTX-I from baseline was 70.2% with ibandronate and 6.0% with placebo (difference, -64.2%; 95% confidence interval, -80.3% to -46.2%; p < 0.0001). In women receiving ibandronate, serum CTX-I levels remained consistently below baseline, exhibiting a regular monthly fluctuating pattern of suppression over 6 months. Ibandronate was well-tolerated. Monthly ibandronate decreased serum CTX-I within 3 days. Over 6 months, in women receiving once-monthly ibandronate, serum CTX-I remained suppressed below baseline. A monthly fluctuation, related to time from last dose, was observed.

Consequences of lifetime isolated growth hormone (GH) deficiency and effects of short‐term GH treatment on bone in adults with a mutation in the GHRH‐receptor gene

Growth hormone (GH) influences bone mass maintenance. However, the consequences of lifetime isolated GH deficiency (IGHD) on bone are not well established. We assessed the bone status and the effect of 6 months of GH replacement in GH-naive adults with IGHD due to a homozygous mutation of the GH-releasing hormone (GHRH)-receptor gene (GHRHR). We studied 20 individuals (10 men) with IGHD at baseline, after 6 months of depot GH treatment, and 6 and 12 months after discontinuation of GH. Quantitative ultrasound (QUS) of the heel was performed and serum osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (ICTP) were measured. QUS was also performed at baseline and 12 months later in a group of 20 normal control individuals (CO), who did not receive GH treatment. At baseline, the IGHD group had a lower T-score on QUS than CO (-1.15 +/- 0.9 vs.-0.07 +/- 0.9, P < 0.001). GH treatment improved this parameter, with improvement persisting for 12 months post-treatment (T-score for IGHD = -0.59 +/- 0.9, P < 0.05). GH also caused an increase in serum OC (baseline vs. pGH, P < 0.001) and ICTP (baseline vs. pGH, P < 0.01). The increase in OC was more marked during treatment and its reduction was slower after GH discontinuation than in ICTP. These data suggest that lifetime severe IGHD is associated with significant reduction in QUS parameters, which are partially reversed by short-term depot GH treatment. The treatment induces a biochemical pattern of bone anabolism that persists for at least 6 months after treatment discontinuation.

Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club

Objectives:To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency.Methodology:Consensus meeting generating guidelines for clinical practice after review and discussion of the randomised controlled trials or meta-analyses on the management of osteoporosis in postmenopausal women.Results:Although the correlation between BMD and BTM is statistically significant, BTM cannot be used as predictive markers of BMD in an individual patient. Both are independent predictors of fracture risk, but BTM can only be used as an additional risk factor in the decision to treat. Current data do not support the use of BTM to select the optimal treatment. However, they can be used to monitor treatment efficiency before BMD changes can be evaluated. Early changes in BTM can be used to measure the clinical efficacy of an anti-resorptive treatment and to reinforce patient compliance.Discussion:Determining a threshold of BTM reflecting an optimal long-term effect is not obvious. The objective should be the return to the premenopausal range and/or a decrease at least equal to the least significant change (30%). Preanalytical and analytical variability of BTM is an important limitation to their use. Serum C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen 1 N terminal extension peptide and bone specific alkaline phosphatase (BSALP) appear to be the most suitable.Conclusion:Consensus regarding the use of BTM resulted in guidelines for clinical practice. BMD determines the indication to treat osteoporosis. BTM reflect treatment efficiency and can be used to motivate patients to persist with their medication.

New Automated Multiplex Assay for Bone Turnover Markers in Osteoporosis

Serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), N-terminal propeptide of type I collagen (PINP), and osteocalcin (OC) are among the most sensitive bone turnover markers for evaluating osteoporosis. Each marker is currently measured individually by manual or automated immunoassays that are time consuming and require substantial sample volume. We evaluated the performance characteristics of a novel, fully automated, protein-array chip system that allows the simultaneous measurement of CTX-I, PINP, OC, and intact parathyroid hormone (PTH) in 20 microL of serum. We measured CTX-I, PINP, OC, and PTH using multiplex and corresponding automated single assays in 157 healthy premenopausal women, 74 healthy men, and 56 postmenopausal osteoporotic women before and 6 months after treatment with oral ibandronate (150 mg/month). Within- and between-run CVs of the multiplex assay were similar to those of single measurement assays (<10% for all markers), whereas the limit of quantification was lower, except for OC. Multiplex values highly correlated (r > 0.93, P < 0.0001 for all markers) with the corresponding single assays, and measured concentrations were comparable. After 6 months of ibandronate, CTX-I, PINP, and OC decreased by a median of 48%, 63%, and 52%, respectively (P < 0.0001 for all 3 markers), magnitudes similar to those of the corresponding single assays. The automated protein-array chip demonstrated similar analytical precision, improved analytical sensitivity, and comparable measured concentrations to those of single assays. The multiplex assay should be useful for assessing bone metabolism in large clinical studies, particularly when sample volume is limited.

Prevalence and significance of vitamin D deficiency in multiple myeloma patients

Prevalence and significance of vitamin D deficiency in multiple myeloma patients

Rapid Suppression of Bone Resorption Marker Levels With Ibandronate Therapy in a Bisphosphonate-Naïve Population

This 6-mo open-label study assessed the pattern of bone turnover marker (BTM) level changes in bisphosphonate-naïve women with postmenopausal osteoporosis treated with monthly oral ibandronate 150 mg and the correlation between month 1 and month 6 serum C-terminal cross-linking telopeptide of type I collagen (sCTX) levels. The following BTMs were monitored: sCTX, urinary N-terminal telopeptide of type I collagen (uNTX), serum procollagen type 1 N-terminal propeptide (PINP), serum osteocalcin (OC), and serum bone-specific alkaline phosphatase (bALP). BTM levels were measured immediately before dosing at baseline and months 1, 2, 3, and 6, and 7 d after dosing at baseline and month 4. A multiple regression model was applied to determine whether month 1 sCTX response predicted month 6 sCTX change. sCTX levels declined 70% 7 d after dosing at baseline and month 4. Predosing sCTX declined 55% at month 6. The pattern of uNTX reduction was similar to sCTX. Bone formation markers PINP, OC, and bALP declined gradually over time. Month 1 sCTX change was a significant predictor of Month 6 change ( p = 0.0001). Once monthly 150 mg oral ibandronate treatment reduced BTMs in women with osteoporosis. sCTX reduction occurred within 7 d and was sustained over 6 mo. Month 1 sCTX predicted month 6 sCTX.

Biomarkers of bone health and osteoporosis risk

The assay features of biochemical markers of bone turnover have markedly improved in the past few years. The most sensitive and specific markers of bone formation include serum bone alkaline phosphatase, total osteocalcin (including the intact molecule and the large N-mid fragment) and the procollagen type I N-terminal propeptide assay. Among the various markers of bone resorption, measurements of the urinary excretion of N- and C-terminal cross-linked telopeptides) and of serum C-terminal cross-linked telopeptides are the most sensitive and specific. Markers of bone turnover can be used to predict the rate of bone loss in post-menopausal women and can also be used to assess the risk of fractures. In osteoporosis-treatment studies (with alendronate, risedronate, raloxifene) markers of bone turnover appear even more strongly associated with fracture risk reduction than bone mineral density (BMD). These observations support the use of markers of bone turnover as surrogates for fracture risk reduction, perhaps even more so than BMD. Bone markers can also be used to monitor the efficacy of antiresorptive therapy such as hormone-replacement therapy, raloxifene and bisphosphonates in individual patients. Furthermore, they have also proved to be helpful in monitoring the response to nutritional interventions and have the advantage over BMD in that they provide information about mechanism of effect and changes are often observed much more rapidly.

Collagen telopeptide (serum CTX) and its relationship with the size and number of lesions in osteonecrosis of the jaws in cancer patients on intravenous bisphosphonates

Osteonecrosis of the jaws (ONJ) is an important possible late adverse effect of bisphosphonates. Serum C-terminal cross-linking telopeptide of type I collagen (CTX) can determine bone turnover and can act as a biological marker of bone resorption. We studied this biological marker in 15 patients (Group 1) with bisphosphonate-induced ONJ comparing with a control group of 10 healthy people matched by age and gender. We found no statistically significant relationships in Group 1 either between the serum CTX and the number of areas of exposed bone nor with the size of the osteonecrotic area.

Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis

Background:Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor α (TNFα). Therefore, we tested...

Calcium metabolism and vitamin D in the extreme longevity

Skeletal remodelling is a continuous process during life and is still active also in extreme senescence. In the elderly, bone resorption often prevails over bone formation, causing bone loss and fragility. Elderly subjects are exposed to the risk of fractures, and loss of self-sufficiency, if considering that the proximal femur is the most frequently involved site. Bone remodelling can maintain circulating calcium within physiological ranges, at the expense of a substantial loss of this ion from the skeleton, particularly during senescence. Calcium metabolism is regulated at cellular/molecular level by a network of cytokines, growth factors, systemic hormones that act on bone in paracrine/autocrine/systemic fashion. Among the molecules involved in bone metabolism, parathyroid hormone (PTH) and vitamin D present some peculiar aspects during senescence. The osteometabolic features in a consistent group of centenarians have been evaluated. It results that a severe hypovitaminosis D was present in 99 out of 104 centenarians (25-OH vitamin D below 5 nmol/L), and that it plays an important role as a factor inducing a vicious circle involving hypocalcemia, secondary hyperparathyroidism, together with biochemical features indicating a consistent bone loss. Serum C-terminal cross-linking telopeptide, a specific marker of bone resorption was elevated in 92% of these subjects. Moreover, it has been found that several femoral fractures had occurred after 90 years of age. These data offer a rational for the possible prevention of elevated bone turnover, bone loss and consequently the reduction of osteoporotic fractures and fractures-induced disability, in the oldest olds, through the simple supplementation with calcium and vitamin D.